The present invention relates to an improved therapeutic method for the treatment of chronic uremic patients undergoing periodical hemodialysis.
It is well known that patients affected by chronic uremia, undergoing periodic hemodialysis, frequently develop a clinical picture characterized by marked muscular asthenia and a sensation of torpor, particularly evident immediately following dialysis. These conditions attributed to the loss of carnitine during dialysis may often last for several hours making difficult, if not impossible, to resume working activity until these conditions subside. Clinical experts recognize this problem as xe2x80x9cpost-dialytic syndromexe2x80x9d.
A method for treating post-dialytic syndrome by compensating for the loss of carnitine occurring during the dialysis session is disclosed in U.S. Pat. No. 4,272,549. This patent describes a method for alleviating asthenia and muscle weakness in a chronic uremic patient undergoing regular dialysis treatment by administering to the patient a polysaline dialytic solution which contains a quantity of carnitine (this refers to L-carnitine throughout the present specification), or a pharmaceutically acceptable salt of it, sufficient to adjust the molar concentration of carnitine in the dialysis solution at least equal to the molar concentration of carnitine in the patient""s plasma. Preferably, the concentration of carnitine in the dialytic solution is substantially equimolar to the concentration of carnitine in the patient""s plasma, but a certain excess of carnitine is also provided, for example between 50 and 100xcexc mole per liter of solution. A specific illustration includes administration of from 3 to 6 grams of carnitine or an equivalent amount of a pharmaceutically acceptable salt thereof. The carnitine may be administered orally, preferably on days between hemodialysis, in amounts ranging from 3 to 6 grams of carnitine per day.
This oral treatment is coupled with a rather complex treatment regimen with carnitine during the course of the dialytic session, in which carnitine is administered by slow infusion. On the days of dialysis, carnitine may also be administered partly by the oral route and partly by slow infusion. In this case, the overall quantity of carnitine administered should not exceed approximately 10 g per day. xe2x80x9cSlow infusionxe2x80x9d means an infusion in which the solution containing carnitine, or any of its pharmaceutically acceptable salts, is administered at the rate of 20 to 40 drops per minute. Particularly favorable therapeutic results are said to be achieved by orally administering carnitine to the patient receiving dialysis treatment only on those days during which the patient does not receive dialysis, while during the actual dialytic session, a dialyzing liquid containing carnitine is used.
A preferred regimen for treating chronic uremic patients undergoing hemodialysis, includes the following steps:
1) on the days between one hemodialytic session and the next, oral administration to these patients of 3 to 6 g per day of carnitine or any of its pharmaceutically acceptable salts;
2) on the days of hemodialytic session, dialyzing these patients using, as a dialyzing liquid, a solution containing a quantity of carnitine or of any of its pharmaceutically acceptable salts, sufficient to adjust the molar concentration of carnitine in the dialysis solution at least equal to the molar concentration of the plasma carnitine of the patient receiving dialytic treatment.
Using this procedure, it is possible to avoid the loss of plasma carnitine which otherwise takes place during a hemodialytic session; that is, the concentration of plasma carnitine remains practically unchanged during the dialytic session. In this manner, it is possible to avoid tissue carnitine depletion, which is a long-term consequence of repeated losses of camitine the patient undergoes during successive dialytic sessions over a prolonged period of time, for example, a month or two or longer.
Although the desired objective is achieved using a hemodialysis solution equimolar in carnitine with respect to the patient""s blood, it is preferred to operate with a slightly more concentrated solution. In practice, the hemodialysis solution contains 50 to 100, preferably 60-80 xcexcmoles/liter of carnitine or of any of its pharmaceutically acceptable salts. On the days of hemodialysis, carnitine may also be administered partly by the oral route and partly by slow infusion. In this case, the overall quantity of carnitine administered will not exceed approximately 10 g per day.
The procedures in U.S. Pat. No. 4,272,549 are effective in treating xe2x80x9cpost-dialysis syndromexe2x80x9d, but present a cumbersome schedule of treatment. This fact leads to problems. Patient compliance, whose quality of life is already heavily affected, is a concern as patients are apt to overlook the oral self administration of a prescribed dosage of carnitine between the dialytic sessions. There is also the problem of carnitine bioavailability through the oral route, which is subject to a saturation mechanism and to other restrictions as to the absorption sites (Harper at al. Eur. J. Clin. Pharmacol. 1988; 35(5):555-62 and Matsuda Et Al. Biol Pharm. Bull 1998, Jul; 21 (7):752-5). Also, oral administration of carnitine to a chronic uremic patient may give rise to the accumulation of toxic metabolites.
A recent article by Sloan et al. (Am. J. Kidney Dis. 1998, August; 32(2):265-72) demonstrated that oral supplementation of carnitine is effective in improving the quality of life of patients in the early stage of treatment, but the perceived beneficial effect was not sustained through long term treatment (six months).
Disclosed is a method for treating chronic uremic patients undergoing periodic hemodialysis. This method prevents and treats carnitine deficiency in patients with end stage renal disease who are undergoing dialysis. The method comprises administering to the dialysis patient an effective dose of carnitine intravenously into the venous return line at the conclusion of each dialysis session. Dialysis session as used herein means both hemodialysis and peritoneal dialysis.
The method of the present invention provides a surprising improvement over the procedures described in U.S. Pat. No. 4,272,549 and eliminates the need for oral treatment, without affecting the maintenance or correction of carnitine deficiency obtained by the administration of carnitine through intravenous route.
The invention shall be disclosed in further detail, with reference to Figures and Examples.